Charles River has developed several relevant two-drug combination formats to be run using 47 PDX-derived cell lines. The formats include two drugs combined in a fixed-ratio or fixed-concentration format. The format used depends on the mechanism of action of the drugs or compounds, if known, and on whether these compounds are mutually exclusive or non-exclusive.
Combination studies are initially run in pre-screen mode, which includes three-point concentration steps, followed by further evaluation in 5 or 10 concentration modes to obtain synergy and/or antagonism values. Alternatively, the detailed format can be applied immediately to obtain data on synergy and/or antagonism.
We have integrated the well-known Chou-Talalay method, a linear model-based combination analysis tool, and the nonlinear model-based method developed by Zhao et al. Currently, we are working on integrating Bliss independence in our combination analysis portfolio. We recommend using at least two of these tools to evaluate combinations of synergy and antagonism.